tbuckley/cabot-search huggingface dataset:
The Royal College of Physicians of London, Portraits.
Journal: Annals of Internal Medicine (1979)

Reviewsbutryaceous fluid is very often present, which rising to the top of its serum, in conjunction with the caseous-like principle of which we have been speaking, forms an appearance exactly resembling the cream of milk; and these principles are often so abundant, especially in the chyle of animals fed on flesh, that, as Dr. Marcet has observed, they may be readily detected, even in the blood itself.Vauquelin remarked the near resemblance of this fatty matter to that which he had extracted from the brain, and I made the same remark before I had seen Vauquelin's paper.....1 It may prove possible to identify other reviews as Elliotson's, for books on animal magnetism and the doctrines of Gall and Spurzheim were analysed.
Relation of Virus-Induced Cell Fusion and Chromosome Pulverization to Mitotic Events&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1969)

The chromosome pulverization phenomenon was studied in a Chinese hamster cell line during the initial period of Sendai virus infection. Cell fusion occurred immediately after virus infection, and the frequency of multinucleate cells leveled of within 25 minutes. However, chromosome pulverization was detected for the first time 10 minutes after virus infection, and the incidence rose until 45 minutes. In most cases, pulverization occurred in multinucleate cells having at least one apparently intact mitotic nucleus ranging from metaphase to telophase. The incidence of pulverization suddenly fell to about one-fourth the maximum value by 60 minutes after virus infection. Autoradiographic examination revealed that the nucleus was susceptible to the pulverization-inducing factor(s) during either G1, S, or G2, possibly including early mitosis. The variability in morphology of the pulverized sets was explained in terms of the cellular stage in which the nucleus had been affected and the length of exposure of the nucleus to the virus. The presence of an intact mitotic nucleus in the cells with pulverization not only confirmed the concept that cell fusion is a prerequisite for pulverization induction, but further suggested a possibly active role played by the mitotic nucleus with its cytoplasm in pulverization induction.
Kawasaki Syndrome: Still a Mystery After 20 Years
Authors: David M. Bell
Journal: JAMA (1985)

It has become unusual in modern medicine for a serious, presumably infectious disease to defy virtually all efforts at elucidation of its etiology and pathogenesis and to leave unanswered, after two decades, so many questions about therapy and prognosis. Other newly described mysteries, including legionnaires' disease, toxic shock syndrome, Lyme disease, and even the acquired immunodeficiency syndrome, have been solved, or at least "demystified," with impressive regularity, but Kawasaki syndrome has not. Kawasaki syndrome was first described in the 1960s in Japan, where it continues to be highly prevalent.<sup>1</sup>A decade later, cases were recognized (independently) in Hawaii,<sup>2</sup>and in recent years, epidemics have occurred in several American cities.<sup>3</sup>Primarily affecting young children, the disease is characterized by fever, conjunctival injection, oropharyngeal inflammation, peripheral extremity changes (edema, erythema, and desquamation), rash, and cervical lymphadenopathy. Coronary artery aneurysms have been present in 7% to 40% of cases, with an
Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma
Authors: Nicole Thomas, Kostiantyn Dreval, Daniela S. Gerhard, Laura K. Hilton, Jeremy S. Abramson, Richard F. Ambinder, Stefan Barta, Nancy L. Bartlett, Jeffrey Bethony, Kishor Bhatia, Jay Bowen, Anthony C. Bryan, Ethel Cesarman, Corey Casper, Amy Chadburn, Manuela Cruz, Dirk P. Dittmer, Maureen A. Dyer, Pedro Farinha, Julie M. Gastier-Foster, Alina S. Gerrie, Bruno M. Grande, Timothy Greiner, Nicholas B. Griner, Thomas G. Gross, Nancy L. Harris, John D. Irvin, Elaine S. Jaffe, David Henry, Rebecca Huppi, Fabio E. Leal, Michael S. Lee, Jean Paul Martin, Marie-Reine Martin, Sam M. Mbulaiteye, Ronald Mitsuyasu, Vivian Morris, Charles G. Mullighan, Andrew J. Mungall, Karen Mungall, Innocent Mutyaba, Mostafa Nokta, Constance Namirembe, Ariela Noy, Martin D. Ogwang, Abraham Omoding, Jackson Orem, German Ott, Hilary Petrello, Stefania Pittaluga, James D. Phelan, Juan Carlos Ramos, Lee Ratner, Steven J. Reynolds, Paul G. Rubinstein, Gerhard Sissolak, Graham Slack, Shaghayegh Soudi, Steven H. Swerdlow, Alexandra Traverse-Glehen, Wyndham H. Wilson, Jasper Wong, Robert Yarchoan, Jean C. ZenKlusen, Marco A. Marra, Louis M. Staudt, David W. Scott, Ryan D. Morin
Journal: Blood (2022)

Abstract Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.
Murine allogeneic CAR T cells integrated before or early after posttransplant cyclophosphamide exert antitumor effects
Authors: Michael T. Patterson, Shanzay M. Khan, Natalia S. Nunes, Rochelle E. Fletcher, Jing Bian, Ashley D. Hadjis, Michael A. Eckhaus, Suresh K. Mendu, Alessandra de Paula Pohl, David J. Venzon, Hyoyoung Choo-Wosoba, Kazusa Ishii, Haiying Qin, Terry J. Fry, Maggie Cam, Christopher G. Kanakry
Journal: Blood (2022)

Relapse limits the therapeutic efficacy both of chimeric antigen receptor (CAR) T cells and allogeneic hematopoietic cell transplantation (allo-HCT). Patients may undergo these therapies sequentially to prevent or treat relapsed malignancy. However, direct integration of the 2 therapies has been avoided over concerns for potential induction of graft-versus-host disease (GVHD) by allogeneic CAR T cells. We have shown in murine T-cell-replete MHC-haploidentical allo-HCT that suppressive mechanisms induced immediately after posttransplant cyclophosphamide (PTCy), given on days +3/+4, prevent GVHD induction by alloreactive T cells infused as early as day +5. Therefore, we hypothesized that allogeneic CAR T cells given in a similarly integrated manner in our murine MHC-haploidentical allo-HCT model may safely exert antitumor effects. Indeed, allogeneic anti-CD19 CAR T cells given early after (day +5) PTCy or even prior to (day 0) PTCy cleared leukemia without exacerbating the cytokine release syndrome occurring from the MHC-haploidentical allo-HCT or interfering with PTCy-mediated GVHD prevention. Meanwhile, CAR T-cell treatment on day +9 or day +14 was safe but less effective, suggesting a limited therapeutic window. CAR T cells infused before PTCy were not eliminated, but surviving CAR T cells continued to proliferate highly and expand despite PTCy. In comparison with infusion on day +5, CAR T-cell infusion on day 0 demonstrated superior clinical efficacy associated with earlier CAR T-cell expansion, higher phenotypic CAR T-cell activation, less CD4+CD25+Foxp3+ CAR T-cell recovery, and transcriptional changes suggesting increased activation of CD4+ CAR T cells and more cytotoxic CD8+ CAR T cells. This study provides mechanistic insight into PTCy's impact on graft-versus-tumor immunity and describes novel approaches to integrate CAR T cells and allo-HCT that may compensate for deficiencies of each individual approach.
Impact of an Interdisciplinary Goals-of-Care Program Among Medical Inpatients at a Comprehensive Cancer Center During the COVID-19 Pandemic: A Propensity Score Analysis
Authors: David Hui, Nico Nortje, Marina George, Kaycee Wilson, Diana L. Urbauer, Caitlin A. Lenz, Susannah Kish Wallace, Clark R. Andersen, Tito Mendoza, Sajid Haque, Sairah Ahmed, Marvin Delgado-Guay, Shalini Dalal, Nisha Rathi, Akhila Reddy, Jennifer McQuade, Christopher Flowers, Peter Pisters, Thomas Aloia, Eduardo Bruera
Journal: Journal of Clinical Oncology (2022)

PURPOSE Many hospitals have established goals-of-care programs in response to the coronavirus disease 2019 pandemic; however, few have reported their outcomes. We examined the impact of a multicomponent interdisciplinary goals-of-care program on intensive care unit (ICU) mortality and hospital outcomes for medical inpatients with cancer. METHODS This single-center study with a quasi-experimental design included consecutive adult patients with cancer admitted to medical units at the MD Anderson Cancer Center, TX, during the 8-month preimplementation (May 1, 2019-December 31, 2019) and postimplementation period (May 1, 2020-December 31, 2020). The primary outcome was ICU mortality. Secondary outcomes included ICU length of stay, hospital mortality, and proportion/timing of care plan documentation. Propensity score weighting was used to adjust for differences in potential covariates, including age, sex, cancer diagnosis, race/ethnicity, and Sequential Organ Failure Assessment score. RESULTS This study involved 12,941 hospitalized patients with cancer (pre n = 6,977; post n = 5,964) including 1,365 ICU admissions (pre n = 727; post n = 638). After multicomponent goals-of-care program initiation, we observed a significant reduction in ICU mortality (28.2% v 21.9%; change −6.3%, 95% CI, −9.6 to −3.1; P = .0001). We also observed significant decreases in length of ICU stay (mean change −1.4 days, 95% CI, −2.0 to −0.7; P &lt; .0001) and in-hospital mortality (7% v 6.1%, mean change −0.9%, 95% CI, −1.5 to −0.3; P = .004). The proportion of hospitalized patients with an in-hospital do-not-resuscitate order increased significantly from 14.7% to 19.6% after implementation (odds ratio, 1.4; 95% CI, 1.3 to 1.5; P &lt; .0001), and do-not-resuscitate order was established earlier (mean difference −3.0 days, 95% CI, −3.9 to −2.1; P &lt; .0001). CONCLUSION This study showed improvement in hospital outcomes and care plan documentation after implementation of a system-wide, multicomponent goals-of-care intervention.
Treatment of erythema migrans with doxycycline for 7 days versus 14 days in Slovenia: a randomised open-label non-inferiority trial
Authors: Daša Stupica, Stefan Collinet-Adler, Rok Blagus, Anja Gomišček, Tjaša Cerar Kišek, Eva Ružić-Sabljić, Maša Velušček
Journal: The Lancet Infectious Diseases (2022)
WHO's Therapeutics and COVID-19 Living Guideline on mAbs needs to be reassessed
Authors: Mary Y Wu, Edward J Carr, Ruth Harvey, Harriet V Mears, Svend Kjaer, Hermaleigh Townsley, Agnieszka Hobbs, Martina Ragno, Lou S Herman, Lorin Adams, Steve Gamblin, Michael Howell, Rupert Beale, Michael Brown, Bryan Williams, Sonia Gandhi, Charles Swanton, Emma C Wall, David L V Bauer
Journal: The Lancet (2022)
Tumor-Derived Extracellular Vesicles: Multifunctional Entities in the Tumor Microenvironment
Authors: James W. Clancy, Crislyn D'Souza-Schorey
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

Tumor cells release extracellular vesicles (EVs) that can function as mediators of intercellular communication in the tumor microenvironment. EVs contain a host of bioactive cargo, including membrane, cytosolic, and nuclear proteins, in addition to noncoding RNAs, other RNA types, and double-stranded DNA fragments. These shed vesicles may deposit paracrine information and can also be taken up by stromal cells, causing the recipient cells to undergo phenotypic changes that profoundly impact diverse facets of cancer progression. For example, this unique form of cellular cross talk helps condition the premetastatic niche, facilitates evasion of the immune response, and promotes invasive and metastatic activity. These findings, coupled with those demonstrating that the number and content of EVs produced by tumors can vary depending on their tumor of origin, disease stage, or response to therapy, have raised the exciting possibility that EVs can be used for risk stratification, diagnostic, and even prognostic purposes. We summarize recent developments and the current knowledge of EV cargoes, their impact on disease progression, and implementation of EV-based liquid biopsies as tumor biomarkers.
Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial
Authors: Sagar Lonial, Rakesh Popat, Cyrille Hulin, Sundar Jagannath, Albert Oriol, Paul G Richardson, Thierry Facon, Katja Weisel, Jeremy T Larsen, Monique C Minnema, Al-Ola Abdallah, Ashraf Z Badros, Stefan Knop, Edward A Stadtmauer, Yiming Cheng, Michael Amatangelo, Min Chen, Tuong Vi Nguyen, Alpesh Amin, Teresa Peluso, Niels W C J van de Donk
Journal: The Lancet Haematology (2022)
An Aspirin a Day: New Pharmacological Developments and Cancer Chemoprevention
Authors: David G. Menter, Robert S. Bresalier
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Chemoprevention refers to the use of natural or synthetic agents to reverse, suppress, or prevent the progression or recurrence of cancer. A large body of preclinical and clinical data suggest the ability of aspirin to prevent precursor lesions and cancers, but much of the clinical data are inferential and based on descriptive epidemiology, case control, and cohort studies or studies designed to answer other questions (e.g., cardiovascular mortality). Multiple pharmacological, clinical, and epidemiologic studies suggest that aspirin can prevent certain cancers but may also cause other effects depending on the tissue or disease and organ site in question. The best-known biological targets of aspirin are cyclooxygenases, which drive a wide variety of functions, including hemostasis, inflammation, and immune modulation. Newly recognized molecular and cellular interactions suggest additional modifiable functional targets, and the existence of consensus molecular cancer subtypes suggests that aspirin may have differential effects based on tumor heterogeneity. This review focuses on new pharmacological developments and innovations in biopharmacology that clarify the potential role of aspirin in cancer chemoprevention.
Understanding the Chemical Exposome During Fetal Development and Early Childhood: A Review
Authors: Magdaléna Krausová, Dominik Braun, Tina Buerki-Thurnherr, Claudia Gundacker, Eva Schernhammer, Lukas Wisgrill, Benedikt Warth
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Early human life is considered a critical window of susceptibility to external exposures. Infants are exposed to a multitude of environmental factors, collectively referred to as the exposome. The chemical exposome can be summarized as the sum of all xenobiotics that humans are exposed to throughout a lifetime. We review different exposure classes and routes that impact fetal and infant metabolism and the potential toxicological role of mixture effects. We also discuss the progress in human biomonitoring and present possiblemodels for studying maternal-fetal transfer. Data gaps on prenatal and infant exposure to xenobiotic mixtures are identified and include natural biotoxins, in addition to commonly reported synthetic toxicants, to obtain a more holistic assessment of the chemical exposome. We highlight the lack of large-scale studies covering a broad range of xenobiotics. Several recommendations to advance our understanding of the early-life chemical exposome and the subsequent impact on health outcomes are proposed.
Automated Insulin Delivery: Benefits, Challenges, and Recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association
Authors: Jennifer L. Sherr, Lutz Heinemann, G. Alexander Fleming, Richard M. Bergenstal, Daniela Bruttomesso, Hélène Hanaire, Reinhard W. Holl, John R. Petrie, Anne L. Peters, Mark Evans
Journal: Diabetes Care (2022)

A technological solution for the management of diabetes in people who require intensive insulin therapy has been sought for decades. The last 10 years have seen substantial growth in devices that can be integrated into clinical care. Driven by the availability of reliable systems for continuous glucose monitoring, we have entered an era in which insulin delivery through insulin pumps can be modulated based on sensor glucose data. Over the past few years, regulatory approval of the first automated insulin delivery (AID) systems has been granted, and these systems have been adopted into clinical care. Additionally, a community of people living with type 1 diabetes has created its own systems using a do-it-yourself approach by using products commercialized for independent use. With several AID systems in development, some of which are anticipated to be granted regulatory approval in the near future, the joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association has created this consensus report. We provide a review of the current landscape of AID systems, with a particular focus on their safety. We conclude with a series of recommended targeted actions. This is the fourth in a series of reports issued by this working group. The working group was jointly commissioned by the executives of both organizations to write the first statement on insulin pumps, which was published in 2015. The original authoring group was comprised by three nominated members of the American Diabetes Association and three nominated members of the European Association for the Study of Diabetes. Additional authors have been added to the group to increase diversity and range of expertise. Each organization has provided a similar internal review process for each manuscript prior to submission for editorial review by the two journals. Harmonization of editorial and substantial modifications has occurred at both levels. The members of the group have selected the subject of each statement and submitted the selection to both organizations for confirmation.
Cancer risk in patients with diverticular disease: A nationwide cohort study
Authors: Wenjie Ma, Marjorie M Walker, Marcus Thuresson, Bjorn Roelstraete, Filip Sköldberg, Ola Olén, Lisa L Strate, Andrew T Chan, Jonas F Ludvigsson
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background There are little data on diverticular disease and cancer development other than colorectal cancer. Methods We conducted a population-based, matched cohort study with linkage of nationwide registers to the Epidemiology Strengthened by histoPathology Reports in Sweden histopathology cohort. We included 75 704 patients with a diagnosis of diverticular disease and colorectal histopathology and 313 480 reference individuals from the general population matched on age, sex, calendar year, and county. Cox proportional hazards models estimated multivariable-adjusted hazard ratios (HRs) for associations between diverticular disease and overall cancer and specific cancers. Results Over a median follow-up of 6 years, we documented 12 846 incident cancers among patients with diverticular disease and 43 354 incident cancers among reference individuals from the general population. Compared with reference individuals, patients with diverticular disease had statistically significantly increased overall cancer incidence (24.5 vs 18.1 per 1000 person-years), equivalent to 1 extra cancer case in 16 individuals with diverticular disease followed-up for 10 years. After adjusting for covariates, having a diagnosis of diverticular disease was associated with a 33% increased risk of overall cancer (95% confidence interval [CI] = 1.31 to 1.36). The risk increases also persisted compared with siblings as secondary comparators (HR = 1.26, 95% CI = 1.21 to 1.32). Patients with diverticular disease also had an increased risk of specific cancers, including colon cancer (HR = 1.71, 95% CI = 1.60 to 1.82), liver cancer (HR = 1.72, 95% CI = 1.41 to 2.10), pancreatic cancer (HR = 1.62, 95% CI = 1.42 to 1.84), and lung cancer (HR = 1.50, 95% CI = 1.39 to 1.61). The increase in colorectal cancer risk was primarily restricted to the first year of follow-up, and especially early cancer stages. Conclusions Patients with diverticular disease who have colorectal histopathology have an increased risk of overall incident cancer.
Technology and Mental Health: State of the Art for Assessment and Treatment
Authors: Philip D. Harvey, Colin A. Depp, Albert A. Rizzo, Gregory P. Strauss, David Spelber, Linda L. Carpenter, Ned H. Kalin, John H. Krystal, William M. McDonald, Charles B. Nemeroff, Carolyn I. Rodriguez, Alik S. Widge, John Torous
Journal: American Journal of Psychiatry (2022)

Technology is ubiquitous in society and is now being extensively used in mental health applications. Both assessment and treatment strategies are being developed and deployed at a rapid pace. The authors review the current domains of technology utilization, describe standards for quality evaluation, and forecast future developments. This review examines technology-based assessments of cognition, emotion, functional capacity and everyday functioning, virtual reality approaches to assessment and treatment, ecological momentary assessment, passive measurement strategies including geolocation, movement, and physiological parameters, and technology-based cognitive and functional skills training. There are many technology-based approaches that are evidence based and are supported through the results of systematic reviews and meta-analyses. Other strategies are less well supported by high-quality evidence at present, but there are evaluation standards that are well articulated at this time. There are some clear challenges in selection of applications for specific conditions, but in several areas, including cognitive training, randomized clinical trials are available to support these interventions. Some of these technology-based interventions have been approved by the U.S. Food and Drug administration, which has clear standards for which types of applications, and which claims about them, need to be reviewed by the agency and which are exempt.